Osmotically Balanced Barriers for Leak-Resistant Nanopore Sequencing
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Solution Overview
Problem
Existing devices and methods for polynucleotide sequencing, such as those using nanopores, are not sufficiently robust, reproducible, or sensitive for practical commercial applications like genome sequencing, particularly in clinical settings, due to issues with osmotic pressure imbalances that can weaken barriers and lead to leakage.
Innovation Solution
The implementation of osmotically balanced barriers, where opposing osmotic pressures are used to stabilize the barrier by maintaining a difference in salt concentrations across the barrier, with a compound in one side to counteract the osmotic pressure, ensuring stability and functionality during sequencing operations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a difference in salt concentration is maintained across the barrier to enable sequencing operations, then the osmotic pressure difference improves ion flow and sequencing sensitivity, but the barrier becomes unstable and may leak due to unbalanced osmotic pressure
Solution Approach 1:
The patent introduces a second compound (e.g., PEG, sugar, or protein) on the trans side of the barrier that generates osmotic pressure opposing the salt concentration gradient. This counterbalancing osmotic pressure prevents barrier instability and leakage while maintaining the salt concentration difference necessary for ion flow and sequencing sensitivity. The second compound acts as a counterweight to the osmotic force generated by the salt gradient.
2Measurement precision
If the barrier is made thinner to improve signal detection, then measurement sensitivity increases, but the barrier becomes more susceptible to osmotic pressure damage and leakage
Solution Approach 1:
The counterbalancing compound generates osmotic pressure that offsets the stress on the thin barrier caused by the salt concentration gradient. This allows the barrier to be made thinner for improved signal detection without sacrificing integrity, as the osmotic stresses are neutralized by the opposing osmotic pressure from the second compound.
3Productivity
If the salt concentration on the trans side is increased to improve current signal, then sequencing throughput improves, but osmotic pressure imbalance weakens the barrier and causes leakage
Solution Approach 1:
The second compound (PEG, sugar, or protein) on the trans side generates osmotic pressure that counterbalances the increased salt concentration gradient. This allows higher trans-side salt concentrations to be used for improved current signal and sequencing throughput without compromising barrier stability, as the osmotic forces are equilibrated.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach enhances the stability and longevity of the barriers, allowing for more reliable and efficient polynucleotide sequencing by maintaining barrier integrity and enabling prolonged use in sequencing-by-synthesis processes.
Implementation Method 1
The difference between the first and second concentrations of the salt may generate a first osmotic pressure across the barrier. The concentration of the compound may generate a second osmotic pressure across the barrier that opposes and substantially balances the first osmotic pressure.
Data Source
AI summary
Devices including osmotically balanced barriers, and methods of making and using the same, are provided herein. A fluidic well may include a barrier having first and second sides. A first fluid within the fluidic well may contact the first side of the barrier, and may have a first composition including a first concentration of a salt. A second fluid within the fluidic well may contact the second side of the barrier and may have a second composition including a second concentration of the salt that is different than the first concentration. The difference between the first and second concentrations of the salt may generate a first osmotic pressure across the barrier. The second composition further may include a concentration of a compound other than the salt. The concentration of the compound may generate a second osmotic pressure across the barrier that opposes and substantially balances the first osmotic pressure.